The cepha antibiotics cefoxitin and cephalotin cause a positive interference with the Jaffee' reaction for creatinine. The interference is method dependent. Our studies have shown that the molar absorptivity of the cefoxitin chromophore is 80 percent and the cephalothin chromophore 20 percent of the creatinine chromophore. The rate of reaction is about 1/20 that of creatinine. The equilibrium constants of the antibiotics are about 1/10 that of the creatinine picrate reactions.